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International Journal of Audiology Sep 2018Define clinical trials and adverse event (AE) monitoring from the perspective of the audiologist. Rationalise the importance of audiology's involvement before, during...
OBJECTIVES
Define clinical trials and adverse event (AE) monitoring from the perspective of the audiologist. Rationalise the importance of audiology's involvement before, during and after monitoring. Identify strengths and weaknesses in toxicity grading scales, and discuss factors that may influence these.
DESIGN
Literature involving commonly cited grading scales used to capture ototoxicity is reviewed. Current regulations and language associated with clinical trial implementation and AE monitoring are described. Personal observations based on a variety of clinical populations are drawn from years of experience developing and employing ototoxicity monitoring protocols in a complex medical setting.
RESULTS
Six commonly used grading scales for ototoxicity are systematically reviewed for strengths and weaknesses. Necessary considerations that inform selection of grading scales are presented. A review of and historical context for clinical trial development and AE monitoring is provided.
CONCLUSIONS
The audiologist's role in therapeutic decision making goes beyond collection of the audiogram. Clear communication to stakeholders in ototoxicity monitoring is paramount, and toxicity grading scales are one tool to facilitate this exchange. Various factors should be considered in advance of selecting the most appropriate scale to capture hearing loss, and no scale is without limitation.
Topics: Adverse Drug Reaction Reporting Systems; Age Factors; Attitude of Health Personnel; Audiologists; Clinical Decision-Making; Clinical Trials as Topic; Dose-Response Relationship, Drug; Drug Monitoring; Health Knowledge, Attitudes, Practice; Hearing; Hearing Loss; Hearing Tests; Humans; Predictive Value of Tests; Professional Role; Prognosis; Reproducibility of Results; Research Design; Risk Factors; Severity of Illness Index
PubMed: 29276851
DOI: 10.1080/14992027.2017.1417644 -
The Journal of Antimicrobial... Jul 2024Aminoglycosides (AGs) are important antibiotics in the treatment of Gram-negative sepsis. However, they are associated with the risk of irreversible sensorineural...
BACKGROUND
Aminoglycosides (AGs) are important antibiotics in the treatment of Gram-negative sepsis. However, they are associated with the risk of irreversible sensorineural hearing loss (SNHL). Several genetic variants have been implicated in the development of ototoxicity.
OBJECTIVES
To evaluate the pharmacogenetic determinants of AG-related ototoxicity.
METHODS
This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses and was registered on Prospero (CRD42022337769). In Dec 2022, PubMed, Cochrane Library, Embase and MEDLINE were searched. Included studies were those reporting original data on the effect of the AG-exposed patient's genome on the development of ototoxicity.
RESULTS
Of 10 202 studies, 31 met the inclusion criteria. Twenty-nine studies focused on the mitochondrial genome, while two studied the nuclear genome. One study of neonates found that 30% of those with the m.1555A > G variant failed hearing screening after AG exposure (level 2 evidence). Seventeen additional studies found the m.1555A > G variant was associated with high penetrance (up to 100%) of SNHL after AG exposure (level 3-4 evidence). Nine studies of m.1494C > T found the penetrance of AG-related SNHL to be up to 40%; however, this variant was also identified in those with SNHL without AG exposure (level 3-4 evidence). The variants m.1005T > C and m.1095T > C may be associated with AG-related SNHL; however, further studies are needed.
CONCLUSIONS
This review found that the m.1555A > G and m.1494C > T variants in the MT-RNR1 gene have the strongest evidence in the development of AG-related SNHL, although study quality was limited (level 2-4). These variants were associated with high penetrance of a SNHL phenotype following AG exposure.
Topics: Humans; Aminoglycosides; Ototoxicity; Anti-Bacterial Agents; Pharmacogenetics; Hearing Loss, Sensorineural
PubMed: 38629462
DOI: 10.1093/jac/dkae106 -
Head & Neck Feb 2015Both radiotherapy (RT) and cisplatin-based chemoradiotherapy (CRT) in patients with head and neck cancer may cause sensorineural hearing loss (SNHL). The purpose of this... (Review)
Review
BACKGROUND
Both radiotherapy (RT) and cisplatin-based chemoradiotherapy (CRT) in patients with head and neck cancer may cause sensorineural hearing loss (SNHL). The purpose of this review was to provide more insight into SNHL because of CRT compared to RT.
METHODS
Comprehensive search of Medline and Embase with the terms "radiotherapy" combined with "ototoxicity," "head and neck squamous cell carcinoma," and synonyms.
RESULTS
Of the 2507 studies found, 21 were included in this study. Pooled analysis could not be committed because of heterogeneity. Incidence rates of SNHL after RT and CRT varied considerably, with percentages ranging from 0% to 43% and 17% to 88%, respectively. Factors that influenced the risk of SNHL were radiation dose to the cochlea, follow-up time, age, baseline hearing level, and cisplatin dose.
CONCLUSION
The wide range of SNHL incidence rates makes it impossible to draw any conclusions on the severity of RT- and CRT-induced ototoxicity. To allow for future comparison of study outcomes, development of uniform criteria is of utmost importance.
Topics: Age Factors; Antineoplastic Agents; Chemoradiotherapy; Cisplatin; Cochlea; Dose-Response Relationship, Drug; Head and Neck Neoplasms; Hearing Loss, Sensorineural; Humans; Radiotherapy; Radiotherapy Dosage
PubMed: 24478269
DOI: 10.1002/hed.23551 -
Cancer Epidemiology Aug 2022Platinum-based chemotherapeutic agents cisplatin and carboplatin are widely used in cancer treatment worldwide and may result in ototoxic hearing loss. The high... (Meta-Analysis)
Meta-Analysis Review
Platinum-based chemotherapeutic agents cisplatin and carboplatin are widely used in cancer treatment worldwide and may result in ototoxic hearing loss. The high incidence of cancer and salient ototoxic effects of platinum-based compounds pose a global public health threat. The purpose of this study was twofold. First, to estimate the prevalence of ototoxic hearing loss associated with treatment with cisplatin and/or carboplatin via a systematic review and meta-analysis. Second, to estimate the annual global burden of ototoxic hearing loss associated with exposure to cisplatin and/or carboplatin. For the systematic review, three databases were searched (Ovid Medline, Ovid Embase, and Web of Science Core Collection) and studies that reported prevalence of objectively measured ototoxic hearing loss in cancer patients were included. A random effects meta-analysis determined pooled prevalence (95% confidence intervals [CI]) of ototoxic hearing loss overall, and estimates were stratified by treatment and patient attributes. Estimates of ototoxic hearing loss burden were created with published global estimates of incident cancers often treated with platinum-based compounds and cancer-specific treatment rates. Eighty-seven records (n = 5077 individuals) were included in the meta-analysis. Pooled prevalence of ototoxic hearing loss associated with cisplatin and/or carboplatin exposure was 43.17% [CI 37.93-48.56%]. Prevalence estimates were higher for regimens involving cisplatin (cisplatin only: 49.21% [CI 42.62-55.82%]; cisplatin & carboplatin: 56.05% [CI 45.12-66.43%]) versus carboplatin only (13.47% [CI 8.68-20.32%]). Our crude estimates of burden indicated approximately one million individuals worldwide are likely exposed to cisplatin and/or carboplatin, which would result in almost half a million cases of hearing loss per year, globally. There is an urgent need to reduce impacts of ototoxicity in cancer patients. This can be partially achieved by implementing existing strategies focused on primary, secondary, and tertiary hearing loss prevention. Primary ototoxicity prevention via otoprotectants should be a research and policy priority.
Topics: Antineoplastic Agents; Carboplatin; Cisplatin; Hearing Loss; Humans; Neoplasms; Ototoxicity; Platinum
PubMed: 35724557
DOI: 10.1016/j.canep.2022.102203 -
International Journal of Audiology Nov 2019To identify any change in quality of life (QoL) caused by chemotherapy-induced toxicities, such as hearing loss and tinnitus, to provide information in order to improve...
To identify any change in quality of life (QoL) caused by chemotherapy-induced toxicities, such as hearing loss and tinnitus, to provide information in order to improve services and aid clinicians in their decision-making. This systematic review followed the preferred reporting items for systematic reviews and meta-analysis (PRISMA) checklist. The search terms were cancer, platinum-based chemotherapy, ototoxicity and "quality of life". Titles and abstracts, followed by full texts, were screened by two independent researchers. The relevant data were extracted and quality analysis was performed using the NIH Quality Assessment Tool. About 308 titles and abstracts were screened, and 27 full-text articles were screened. Ten articles representing 11 studies were included in the review. Study design included cross-sectional studies, randomised control trials and longitudinal studies. Diagnostic criteria consisted of audiograms, questionnaires and patient complaints. The study quality ranged from 21.43% to 85.71%. Overall results found that those treated with cisplatin had more hearing loss and tinnitus than those treated with other therapies. Furthermore, those with hearing loss and tinnitus were more likely to have a lower QoL. There is an urgent need to standardise diagnostics when investigating ototoxicity and its effect on QoL, particularly for research into risk factors, prevention and management.
Topics: Antineoplastic Agents; Cancer Survivors; Cross-Sectional Studies; Hearing Loss; Humans; Longitudinal Studies; Neoplasms; Ototoxicity; Platinum Compounds; Quality of Life; Randomized Controlled Trials as Topic; Surveys and Questionnaires; Tinnitus
PubMed: 31545660
DOI: 10.1080/14992027.2019.1660918 -
Increased risk of hearing loss associated with macrolide use: a systematic review and meta-analysis.Scientific Reports Jan 2024The increased risk of hearing loss with macrolides remains controversial. We aimed to systematically review and meta-analyze data on the clinical risk of hearing loss,... (Meta-Analysis)
Meta-Analysis
The increased risk of hearing loss with macrolides remains controversial. We aimed to systematically review and meta-analyze data on the clinical risk of hearing loss, tinnitus, and ototoxicity following macrolide use. A systematic search was conducted across PubMed, MEDLINE, Cochrane, and Embase databases from database inception to May 2023. Medical Subject Heading (MeSH) terms and text keywords were utilized, without any language restrictions. In addition to the electronic databases, two authors manually and independently searched for relevant studies in the US and European clinical trial registries and Google Scholar. Studies that involved (1) patients who had hearing loss, tinnitus, or ototoxicity after macrolide use, (2) intervention of use of macrolides such as azithromycin, clarithromycin, erythromycin, fidaxomicin, roxithromycin, spiramycin, and/or telithromycin, (3) comparisons with specified placebos or other antibiotics, (4) outcomes measured as odds ratio (OR), relative risk (RR), hazard ratio (HR), and mean difference for ototoxicity symptoms using randomized control trial (RCT)s and observational studies (case-control, cross-section, and cohort studies) were included. Data extraction was performed independently by two extractors, and a crosscheck was performed to identify any errors. ORs along with their corresponding 95% confidence intervals (CIs) were estimated using random-effects models. The Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guidelines for RCTs and Meta-Analysis of Observational Studies in Epidemiology guidelines for observational studies were followed. We assessed the hearing loss risk after macrolide use versus controls (placebos and other antibiotics). Based on data from 13 studies including 1,142,021 patients (n = 267,546 for macrolide and n = 875,089 for controls), the overall pooled OR was 1.25 (95% CI 1.07-1.47). In subgroup analysis by study design, the ORs were 1.37 (95% CI 1.08-1.73) for RCTs and 1.33 (95% CI 1.24-1.43) for case-control studies, indicating that RCT and case-control study designs showed a statistically significant higher risk of hearing loss. The group with underlying diseases such as multiple infectious etiologies (OR, 1.16 [95% CI 0.96-1.41]) had a statistically significant lower risk than the group without (OR, 1.53 [95% CI 1.38-1.70] P = .013). The findings from this systematic review and meta-analysis suggest that macrolide antibiotics increase the risk of hearing loss and that healthcare professionals should carefully consider this factor while prescribing macrolides.
Topics: Humans; Macrolides; Tinnitus; Ototoxicity; Anti-Bacterial Agents; Hearing Loss; Deafness
PubMed: 38167873
DOI: 10.1038/s41598-023-50774-1 -
Jornal Da Sociedade Brasileira de... 2012To investigate the occurrence of hearing loss in individuals with HIV/AIDS and their characterization regarding type and degree. (Review)
Review
PURPOSE
To investigate the occurrence of hearing loss in individuals with HIV/AIDS and their characterization regarding type and degree.
RESEARCH STRATEGY
It was conducted a systematic review of the literature found on the electronic databases PubMed, EMBASE, ADOLEC, IBECS, Web of Science, Scopus, Lilacs and SciELO.
SELECTION CRITERIA
The search strategy was directed by a specific question: "Is hearing loss part of the framework of HIV/AIDS manifestations?", and the selection criteria of the studies involved coherence with the proposed theme, evidence levels 1, 2 or 3, and language (Portuguese, English and Spanish).
DATA ANALYSIS
We found 698 studies. After an analysis of the title and abstract, 91 were selected for full reading. Out of these, 38 met the proposed criteria and were included on the review.
RESULTS
The studies reported presence of conductive, sensorineural, and mixed hearing loss, of variable degrees and audiometric configurations, in addition to tinnitus and vestibular disorders. The etiology can be attributed to opportunistic infections, ototoxic drugs or to the action of virus itself. The auditory evoked potentials have been used as markers of neurological alterations, even in patients with normal hearing.
CONCLUSION
HIV/AIDS patients may present hearing loss. Thus, programs for prevention and treatment of AIDS must involve actions aimed at auditory health.
Topics: Acquired Immunodeficiency Syndrome; Hearing Loss; Humans; Severity of Illness Index
PubMed: 22832689
DOI: 10.1590/s2179-64912012000200017 -
The International Tinnitus Journal Mar 2021Prevalence of tinnitus range from 7.1% to 14.6% (National Center for Health Statistics, 2016), but the mechanisms responsible for the development of this abnormal...
INTRODUCTION
Prevalence of tinnitus range from 7.1% to 14.6% (National Center for Health Statistics, 2016), but the mechanisms responsible for the development of this abnormal sensory state remain poorly understood.
OBJECTIVES
To determine the evidence for different etiologies and pathophysiology of tinnitus identified by clinical diagnostic tests in the adult population.
STUDY DESIGN
Systematic literature review.
METHODS
Review of data base using PRISMA guidelines: Google Scholar, Medline, Springer Link, Pubmed. In addition, manual reference search of identified papers. Randomized controlled trials, case control study, prospective cohort studies, and retrospective reviews of consecutive patients in which clear data were reported with respect to etiology and pathophysiology of tinnitus.
RESULTS
Sixty seven articles met the inclusion criteria. The papers searched recent studies from 2004 to 2018 for different etiologies such as noise exposure, age, ototoxic drugs, hearing loss among patients with tinnitus. Multiple pathophysiology were identified, including inner ear pathology, auditory nerve synchronisation, central nervous system anomalies and limbic and autonomous nervous system problems. The group of papers evaluated tinnitus patients with specific diagnostic tests such as pure tone audiometry, Immitance audiometry, otoacoustic emission, Auditory brainstem response and diagnostic imaging of fMRI, MRI and PET study.
CONCLUSIONS
The results indicate a high level of heterogeneity between the studies for all the assessed areas. These results support the need for greater stratification of the tinnitus population and the importance of a standardized Puretone audiometry with extended high frequency, OAE, ABR and diagnostic imaging (fMRI, MRI & PET) method to make comparisons between studies possible. Diagnostic imaging is an important useful method for identification of intracranial pathology that can present with tinnitus as a primary symptom. Establishment of a direct causal link between tinnitus and these etiologies and pathophysiology remains elusive.
Topics: Adult; Audiometry, Pure-Tone; Case-Control Studies; Humans; Prospective Studies; Retrospective Studies; Tinnitus
PubMed: 34410084
DOI: 10.5935/0946-5448.20210015 -
Scientific Reports Mar 2019Ototoxicity is one of the major side-effects of platinum-based chemotherapy, in particular cisplatin (cis-diammine dichloroplatinum II). To our knowledge, no systematic... (Meta-Analysis)
Meta-Analysis
Ototoxicity is one of the major side-effects of platinum-based chemotherapy, in particular cisplatin (cis-diammine dichloroplatinum II). To our knowledge, no systematic review has previously provided a quantitative summary estimate of the impact of genetics upon the risk of developing hearing loss. We searched Embase, Medline, ASSIA, Pubmed, Scopus, and Web of Science, for studies documenting the genetic risk of ototoxicity in patients with cancer treated with cisplatin. Titles/abstracts and full texts were reviewed for inclusion. Meta-analytic estimates of risk (Odds Ratio) from the pooled data were calculated for studies that have been repeated twice or more. The search identified 3891 papers, of which 30 were included. The majority were retrospective (44%), ranging from n = 39 to n = 317, some including only patients younger than 25 years of age (33%), and some on both genders (80%). The most common cancers involved were osteosarcoma (53%), neuroblastoma (37%), prostate (17%) and reproductive (10%). Most studies performed genotyping, though only 5 studies performed genome-wide association studies. Nineteen single-nucleotide polymorphisms (SNPs) from 15 genes were repeated more than twice. Meta-analysis of group data indicated that rs1872328 on ACYP2, which plays a role in calcium homeostasis, increases the risk of ototoxicity by 4.61 (95% CI: 3.04-7.02; N = 696, p < 0.0001) as well as LRP2 rs4668123 shows a cumulated Odds Ratio of 3.53 (95% CI: 1.48-8.45; N = 118, p = 0.0059), which could not be evidenced in individual studies. Despite the evidence of heterogeneity across studies, these meta-analytic results from 30 studies are consistent with a view of a genetic predisposition to platinum-based chemotherapy mediated ototoxicity. These new findings are informative and encourage the genetic screening of cancer patients in order to identify patients with greater vulnerability of developing hearing loss, a condition having a potentially large impact on quality of life. More studies are needed, with larger sample size, in order to identify additional markers of ototoxic risk associated with platinum-based chemotherapy and investigate polygenic risks, where multiple markers may exacerbate the side-effects.
Topics: Alleles; Antineoplastic Agents; Cisplatin; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Odds Ratio; Ototoxicity; Pharmacogenomic Variants; Polymorphism, Single Nucleotide; Publication Bias
PubMed: 30837596
DOI: 10.1038/s41598-019-40138-z -
American Journal of Therapeutics 2016Multidrug-resistant tuberculosis (MDR-TB) is a growing public health problem. Due to long duration of therapy and concurrent use of multiple second-line drugs, adverse... (Meta-Analysis)
Meta-Analysis Review
Multidrug-resistant tuberculosis (MDR-TB) is a growing public health problem. Due to long duration of therapy and concurrent use of multiple second-line drugs, adverse drug events (ADEs) are regarded as the most important clinical consideration in patients undergoing anti-MDR-TB treatment. To evaluate the frequency and type of treatment-related ADEs owing to MDR-TB therapy. The Cochrane Library, MEDLINE, and EMBASE were searched from inception through October 1, 2012, with additional manual search of International Journal of Tuberculosis and Lung Disease. Studies with available ADEs were selected if MDR-TB patients were treated with regimen including second-line drugs. Pooled estimations of incidence for each specific type of ADEs were calculated with 95% confidence intervals using random-effects model. Of the 5346 patients included, 2602 (57.3%) experienced at least 1 kind of ADE. The 3 most common side effects were gastrointestinal disorders (32.1%), ototoxicity (14.6%), and psychiatric disorders (13.2%). Subgroup analyses based on each characteristic (study population, previous tuberculosis treated, human immunodeficiency virus prevalence, and length of treatment) did not show any significant difference between groups. Additionally, among 1519 patients who developed ADEs with available data of impact on MDR-TB therapy, 70.4% required change of MDR-TB treatment. Adverse events were common among MDR-TB cases, occurring in more than half of the cases, with over two-thirds requiring change of anti-MDR-TB treatment. MDR-TB patients should be monitored closely and managed aggressively for side effects during therapy, especially for ototoxicity and psychiatric disorders.
Topics: Antitubercular Agents; Databases, Factual; Humans; Tuberculosis, Multidrug-Resistant
PubMed: 24284652
DOI: 10.1097/01.mjt.0000433951.09030.5a